Peripartum asphyxia complicated by moderate or severe hypoxic-ischaemic encephalopathy is a devastating global health issue. A therapeutic 'window of opportunity' exists after resuscitation of the asphyxiated newborn and before the delayed phase of neuronal loss. Animal studies demonstrated that neuronal injury following hypoxia-ischaemia can be prevented or reduced by a mild reduction in brain temperature. Human infant pilot studies confirmed feasibility, without major adverse effects. Randomised trials and systematic reviews comprising term infants with moderate or severe encephalopathy and peripartum asphyxia have established the neuroprotective benefit of therapeutic hypothermia. Hypothermia reduces mortality or major disability to 18 months of age, as well as cerebral palsy, and neuromotor and cognitive delay. Importantly, mortality is reduced without any increase in major neurodevelopmental disability in survivors, and with only minor adverse effects. The evidence supports therapeutic hypothermia when used within strict protocols in tertiary centres to improve the outcome for term and near-term newborns with moderate or severe hypoxic-ischaemic encephalopathy. Equally strict protocols in non-tertiary nurseries will enable earlier initiation of hypothermia under guidance of the regional neonatal intensive care unit and transport team.